Sign up to receive free email alerts when patent applications with chosen keywords are publishedSIGN UP

Abstract:

Various systems and devices for generating nitric oxide are disclosed
herein. According to one embodiment, the device includes a body having an
inlet, an outlet, and a porous solid matrix positioned with the body. The
porous solid matrix is coated with an aqueous solution of an antioxidant,
wherein the inlet is configured to receive a gas flow and fluidly
communicate the gas flow to the outlet through the solid matrix to
convert nitrogen dioxide in the gas flow into nitric oxide. The porous
solid matrix allows the device to be used in any orientation.
Additionally, the porous solid matrix provides a rigid structure suitable
to withstand vibrations and abuse without compromising device
functionality.

Claims:

1-14. (canceled)

15. A device for generating nitric oxide from nitrogen dioxide,
comprising: a receptacle including an inlet, an outlet and a diverter, a
porous solid matrix including an antioxidant positioned within the
receptacle, and a space between the body and the porous solid matrix,
wherein the space has a width, which is the distance between the surface
of the porous solid matrix to the receptacle, and the width of the space
is variable along the length of the receptacle, and wherein the inlet is
configured to receive a gas flow, the diverter directs the gas flow to
the space between the body and the porous solid matrix, and the gas flow
is fluidly communicated to the outlet through the porous solid matrix to
convert nitrogen dioxide in the gas flow into nitric oxide.

16. The device of claim 15, wherein the width of the space decreases
along a portion of the length of the receptacle.

17. The device of claim 15, wherein the width of the space increases
along a portion of the length of the receptacle.

18. The device of claim 15, wherein the width of the space increases
along a portion of the length of the receptacle extending from the inlet
to approximately the midpoint of the receptacle, and the width of the
space decreases along a portion of the length of the receptacle extending
from the approximately the midpoint of the receptacle to the outlet.

19. A system for delivering nitric oxide to a patient, comprising: a gas
source of nitrogen dioxide, dinitrogen tetraoxide, or nitric oxide; a
first device having a receptacle including an inlet, an outlet and a
diverter, a porous solid matrix including an antioxidant positioned
within the receptacle, and a space between the body and the porous solid
matrix, wherein the space has a width, which is the distance between the
surface of the porous solid matrix to the receptacle, and the width of
the space is variable along the length of the receptacle, and wherein the
inlet is configured to receive a gas flow, the diverter directs the gas
flow to the space between the body and the porous solid matrix, and the
gas flow is fluidly communicated to the outlet through the porous solid
matrix to convert nitrogen dioxide in the gas flow into nitric oxide; and
a patient interface coupled to the outlet of the first device, the
patient interface delivering nitric oxide to the patient.

20. The system of claim 19, further comprising a humidifier positioned
between the gas source and the first device.

21. The system of claim 20, wherein the humidifier is integral with the
first device.

22. The system of claim 19, further comprising a humidifier positioned
prior to the patient interface.

23. The system of claim 20, wherein the humidifier has a temperature of
less than 23.degree. C.

24. The system of claim 22, wherein the humidifier has a temperature of
between 32.degree. C. and 37.degree. C.

25. The system of claim 20, further comprising: a second humidifier
positioned after the first device; and a second device positioned after a
second humidifier, the second device having a receptacle including an
inlet, an outlet and a diverter, a porous solid matrix including an
antioxidant positioned within the receptacle, and a space between the
body and the porous solid matrix, wherein the space has a width, which is
the distance between the surface of the porous solid matrix to the
receptacle, and the width of the space is variable along the length of
the receptacle, and wherein the inlet is configured to receive a gas
flow, the diverter directs the gas flow to the space between the body and
the porous solid matrix, and the gas flow is fluidly communicated to the
outlet through the porous solid matrix to convert nitrogen dioxide in the
gas flow into nitric oxide.

Description:

CLAIM OF PRIORITY

[0001] This application claims the benefit of prior U.S. Provisional
Application No. 61/090,614, filed on Aug. 21, 2008, which is incorporated
by reference in its entirety.

TECHNICAL FIELD

[0002] This description relates to systems and devices for generating
nitric oxide.

BACKGROUND

[0003] Nitric oxide (NO), also known as nitrosyl radical, is a free
radical that is an important signaling molecule. For example, NO causes
smooth muscles in blood vessels to relax, thereby resulting in
vasodilation and increased blood flow through the blood vessel. These
effects are limited to small biological regions since NO is highly
reactive with a lifetime of a few seconds and is quickly metabolized in
the body.

[0004] Typically, NO gas is supplied in a bottled gaseous form diluted in
nitrogen gas (N2). Great care has to be taken to prevent the
presence of even trace amounts of oxygen (O2) in the tank of NO gas
because NO, in the presence of O2, is oxidized into nitrogen dioxide
(NO2). Unlike NO, the part per million levels of NO2 gas is
highly toxic if inhaled and can form nitric and nitrous acid in the
lungs.

SUMMARY

[0005] Briefly, and in general terms, various embodiments are directed to
systems and devices for generating nitric oxide (NO). According to one
embodiment, the device includes a body having an inlet, an outlet, and a
porous solid matrix positioned with the body. In one embodiment, the
porous solid matrix is made of a silica gel and a thermoplastic resin.
The porous solid matrix is coated with an aqueous solution of an
antioxidant, wherein the inlet is configured to receive a gas flow and
fluidly communicate the gas flow to the outlet through the porous solid
matrix to convert nitrogen dioxide in the gas flow into nitric oxide. The
porous solid matrix allows the device to be used in any orientation. The
porous solid matrix also provides a rigid structure suitable to withstand
vibrations and abuse associated with shipping and handling.

[0006] In addition to NO-generating devices, various systems for
generating and delivering NO to a patient are disclosed herein. According
to one embodiment, the system includes a gas source including nitrogen
dioxide (NO2), dinitrogen tetraoxide (N2O4), or NO. The
gas source is in communication with a first NO conversion device. The NO
conversion device includes an inlet, an outlet, and a solid matrix coated
with an aqueous solution of an antioxidant positioned between the inlet
and the outlet. The inlet of the NO conversion device is configured to
receive a gas flow from the source and fluidly communicate the gas flow
through the porous solid matrix to the outlet in order to convert
NO2 in the gas flow into NO. The system also includes a patient
interface coupled to the outlet of the first NO conversion device.

[0007] In another embodiment, the system is provided with a second NO
conversion device similar to the first NO conversion device. In this
embodiment, the second NO conversion device is placed in series with the
first NO conversion device, and the patient interface is in communication
with the outlet of the second conversion device. In yet another
embodiment, a humidifier is placed prior to the first conversion device.
In another embodiment, the humidifier is integral with the first
conversion device. Optionally, an active humidifier is placed prior to
the second conversion device.

[0008] Other features will become apparent from the following detailed
description, taken in conjunction with the accompanying drawings, which
illustrate by way of example, the features of the various embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] FIG. 1 is a cross-sectional view of one embodiment of a nitric
oxide (NO) generating device.

[0010] FIG. 2 is a block diagram of one embodiment of a NO generating
device.

[0011] FIG. 3 is a block diagram of one embodiment of a system for
delivering NO to a patient.

DETAILED DESCRIPTION

[0012] Various systems and devices for generating nitric oxide (NO) are
disclosed herein. Generally, NO is inhaled or otherwise delivered to a
patient's lungs. Since NO is inhaled, much higher local doses can be
achieved without concomitant vasodilation of the other blood vessels in
the body. Accordingly, NO gas having a concentration of approximately 10
to approximately 1000 ppm (e.g., greater than 10, 40, 80, 100, 150, 200,
250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900,
950, or 1000 ppm) may be delivered to a patient. Accordingly, high doses
of NO may be used to prevent, reverse, or limit the progression of
disorders which can include, but are not limited to, acute pulmonary
vasoconstriction, traumatic injury, aspiration or inhalation injury, fat
embolism in the lung, acidosis, inflammation of the lung, adult
respiratory distress syndrome, acute pulmonary edema, acute mountain
sickness, post cardiac surgery acute pulmonary hypertension, persistent
pulmonary hypertension of a newborn, perinatal aspiration syndrome,
haline membrane disease, acute pulmonary thromboembolism,
heparin-protamine reactions, sepsis, asthma, status asthmaticus, or
hypoxia. NO can also be used to treat chronic pulmonary hypertension,
bronchopulmonary dysplasia, chronic pulmonary thromboembolism, idiopathic
pulmonary hypertension, primary pulmonary hypertension, or chronic
hypoxia.

[0013] Currently, approved devices and methods for delivering inhaled NO
gas require complex and heavy equipment. NO gas is stored in heavy gas
bottles with nitrogen and no traces of oxygen. NO gas is mixed with air
or oxygen with specialized injectors and complex ventilators, and the
mixing process is monitored with equipment having sensitive
microprocessors and electronics. All this equipment is required in order
to ensure that NO is not oxidized into nitrogen dioxide (NO)) during the
mixing process since NO2 is highly toxic. However, this equipment is
not conducive to use in a non-medical facility setting since the size,
cost, complexity, and safety issues restrict the operation of this
equipment to highly-trained professionals in a medical facility.

[0014] In contrast, the systems and devices disclosed herein do not
require heavy gas bottles, sophisticated electronics, or monitoring
equipment. For example, FIG. 1 illustrates one embodiment of a device 100
that generates NO from NO2. The device 100, which may be referred to
as a NO generation cartridge, a GENO cartridge, a GENO cylinder, or a
recuperator, includes a body 102 having an inlet 104 and an outlet 106.
The inlet 104 and outlet 106 are sized to engage gas plumbing lines or
directly couple to other components such as, but not limited to, gas
tanks, regulators, valves, humidifiers, patient interfaces, or
recuperators. Additionally, the inlet 104 and outlet 106 may include
threads or specially designed fittings to engage these components.

[0015] As shown in FIG. 1, the body 102 is generally cylindrical in shape
and defines a cavity that holds a solid matrix 108. According to one
embodiment, the porous solid matrix 108 is a mixture of a
surface-activated material such as, but not limited to, silica gel and
one or more suitable thermoplastic resins that are sintered at high
temperatures to form a porous solid matrix. The polymers include, but are
not limited to, polyethylene, polypropylene or any thermoplastic resin
that can be ground into a fine powder and the poured into a mold and
sintered at high temperature to form a porous solid matrix. The
thermoplastic resin, when cured, provides a rigid porous structure with
the surface-activated material embedded in the pores. Additionally, the
polymer may be shaped or molded into any form.

[0016] According to one embodiment, the porous solid matrix 108 is
composed of at least 20% silica gel. In another embodiment, the porous
solid matrix 108 includes approximately 20% to approximately 60% silica
gel. In yet another embodiment, the porous solid matrix 108 is composed
of 50% silica gel. As those skilled in the art will appreciate, any ratio
of silica gel to thermoplastic resin is contemplated so long as the
mechanical and structural strength of the porous solid matrix 108 is
maintained. In one embodiment, the densities of the silica gel and the
polymer are generally similar in order to achieve a uniform mixture and,
ultimately, a uniform porous solid matrix 108.

[0017] As shown in FIG. 1, the porous solid matrix 108 also has a
cylindrical shape having an inner bore 112. In other embodiments, the
porous solid matrix may have any shape known or developed in the art. The
porous solid matrix 108 is positioned within the body 102 such that a
space 114 is formed between the body and the porous solid matrix. At the
inlet end 104 of the body 102, a diverter 110 is positioned between the
inlet and the porous solid matrix 108. The diverter 110 directs the gas
flow to the outer diameter of the porous solid matrix 108 (as shown by
the white arrows). Gas flow is forced through the porous solid matrix 108
whereby any NO2 is converted into NO (as shown by the darkened
arrows). NO gas then exits the outlet 106 of the device 100. The porous
solid matrix 108 allows the device 100 to be used in any orientation
(e.g., horizontally, vertically, or at any angle). Additionally, the
porous solid matrix 108 provides a rigid structure suitable to withstand
vibrations and abuse associated with shipping and handling.

[0018] In the device 100 shown in FIG. 1, the pressure drop across the
porous solid matrix 108 is generally less than 1-2 inches of water at a
gas flow rate of 40-60 liters per minute. According to one embodiment,
the porous solid matrix 108 is approximately 10 inches long with an outer
diameter of about 1.3 inches and an inner diameter of about 1 inch. In
alternate embodiments, the porous solid matrix 108 may have different
sizes and diameters based upon the intended use. For example, a portable,
short-term device may have a smaller-sized, porous solid matrix as
compared to a long-term device.

[0019] The body 102 of the device 100 may be made from a polymer, metal,
fiberglass, glass, carbon fiber, ceramic, or other materials known or
developed in the art that is not rapidly corroded or damaged by NO2.
Regardless of the materials used, the construction of the body 102 needs
to be sealed to prevent air from entering the body. Air leakage may occur
because the porous solid matrix 108 has effectively a zero pressure drop,
and air can flow up around the seals of the inlet 104 or outlet 106 and
into the body 102. In order to avoid air leakage into the device 100, the
inside frame of the body 102 holding the solid matrix 108 has a depth
that is greater than the wall thickness of the solid matrix.

[0020] FIG. 2 illustrates another embodiment of a device 200 for
converting NO2 into NO. The device 200 includes a conversion
cartridge 100 and a humidifier 202. The humidifier 202 enhances the
lifetime of the cartridge 100 by replacing moisture in the silica gel
portion of the solid matrix 108. For example, in one experiment, an
unheated humidifier 202 is positioned in the flow line prior to the
cartridge 100. The water temperature in the humidifier dropped from an
ambient temperature of 23° C. to less than 18° C. due to
evaporative cooling. The moisture from the evaporative cooling extended
the life of the cartridge 100 to well over 100 hours whereas a cartridge
without any humidity would have a lifespan of less than 12 hours. If a
humidifier 202 is used with a cartridge 100, the humidity in the
cartridge must be below the dew point. Otherwise, the presence of liquid
water "drowns" the active sites on the silica gel in the device 100,
thereby preventing NO2 gas from interacting with the antioxidant.

[0021] As shown in FIG. 2, the humidifier 202 may be a separate device
placed prior to the cartridge 100. Alternatively, the humidifier 202 and
the cartridge 100 may be an integral component. In one embodiment,
approximately 250 mL of water would be sufficient to maintain the
moisture content in the cartridge 100 well beyond the lifetime of the
porous solid matrix 108. In alternate embodiments, more or less water may
be needed for larger and smaller cartridges, respectively. In other
embodiments (e.g., a short-term device), a humidifier may not be
necessary.

[0022] FIG. 3 illustrates a system 300 for delivering NO to a patient. The
system 300 includes a gas source 302 for generating or containing NO. The
gas source 302 may be a tank of pressurized (or non-pressurized) NO,
NO2, or N2O4. In those systems having a non-pressurized
gas source, a pump is provided to move the gas from the gas source
through the conversion cartridges 306, 310. Optionally, a humidifier 304
or 308 may be placed prior to one or more NO conversion devices 306, 310.

[0023] As shown in FIG. 3, the system 300 includes two conversion devices
306, 310. According to one embodiment, the second conversion device 310
is referred to as a recuperator. The recuperator 310 is identical to the
main conversion device 306 except the recuperator is typically smaller in
size and format. The recuperator 310 is generally smaller for convenience
and to reduce weight and size. Nevertheless, the recuperator 310
functions the same as the main cartridge 306. In alternate embodiments of
the system, the two cartridges 306, 310 may be identical (e.g., two main
cartridges).

[0024] Optionally, the system 300 includes a heated humidifier 308
positioned between the conversion cartridge 310 and the patient interface
312. The patient interface 312 may be a mouth piece, nasal cannula, face
mask, or fully-sealed face mask. According to one embodiment, the
humidifier 308 is a heated humidifier that brings the moisture content up
to a dew point of 32° C. to 37° C. , thereby preventing
moisture loss from the lungs.

[0025] According to one method, the solid matrix is formed by mixing
silica gel with a thermoplastic resin. The mixture is then sintered at a
high temperature to form a porous solid matrix and allowed to cool. After
the porous solid matrix 108 is formed, the porous solid matrix is flushed
with an antioxidant solution. In one embodiment, the antioxidant solution
is approximately 20% ascorbic acid in water. Alternatively, ascorbic acid
may be substituted with other antioxidants such as, but not limited to,
alpha tocopherol or gamma tocopherol. In other embodiments, the
antioxidant solution may have varying antioxidant concentrations.
Dissolved gases (e.g., oxygen and air) are excluded from the antioxidant
solution in order to prevent the formation of microscopic gas bubbles
around the solid polymer/silica gel matrix. The gas bubbles would alter
the surface chemistry and would prevent NO2 from interacting with
the antioxidant liquid inside the silica gel.

[0026] Once the solid matrix 108 has been flushed, the excess antioxidant
solution that is not bound by the silica gel may be rinsed off in order
to minimize the precipitation of excess antioxidant solution during the
drying step. According to one embodiment, the porous solid matrix 108 is
vacuum dried until the moisture content is reduced to approximately 30%.
In alternate embodiments, the solid matrix 108 may be dried to have any
moisture content ranging from approximately 1% to approximately 99%.
During the drying process, precautions need to be taken to ensure that
oxygen is excluded. The dried, solid matrix 108 is assembled into the
body 102 and flushed with inert gas before and during the sealing
process. According to one embodiment, the cartridges 100 are stored in
oxygen and gas-tight containers. Oxygen is excluded from the
manufacturing process and during storage in order to prevent the ascorbic
acid (or other antioxidants) from slowly oxidizing to dehydro-ascorbic
acid and other oxidation products during long-term storage. In another
embodiment, the cartridge is dried until there is no detectable water
present, and the cartridge is then sealed and packaged dry in a
moisture-proof container. The dried cartridge is reconstituted into an
active cartridge by exposing the cartridge to water prior to use.

[0027] The various embodiments described above are provided by way of
illustration only and should not be construed to limit the claimed
invention. Those skilled in the art will readily recognize various
modifications and changes that may be made to the claimed invention
without following the example embodiments and applications illustrated
and described herein, and without departing from the true spirit and
scope of the claimed invention, which is set forth in the following
claims.

Patent applications by Bryan Johnson, Orlando, FL US

Patent applications by David H. Fine, Cocoa Beach, FL US

Patent applications by Gregory Vasquez, Cocoa, FL US

Patent applications in class Gas produced by electrolysis or chemical reaction

Patent applications in all subclasses Gas produced by electrolysis or chemical reaction